Sexual dysfunction is characterized by a disturbance in the processes that are involved in the sexual response cycle or by pain associated with sexual intercourse. The sexual response cycle comprises the four phases of desire, excitement, orgasm and resolution. Disorders of sexual response may occur at one or more of these phases. The sexual dysfunctions include sexual desire disorders, sexual arousal disorders, orgasmic disorders and sexual pain disorders. Sexual dysfunctions cause marked distress and interpersonal difficulty. While progress has been made in the treatment of such disorders, there remains significant need for alternative therapeutic approaches.
A normal erection occurs as a result of a coordinated vascular event in the penis. This is usually triggered neurally and consists of vasodilation and smooth muscle relaxation in the penis and its supplying arterial vessels. Arterial inflow causes enlargement of the substance of the corpora cavernosa. Venous outflow is trapped by this enlargement, permitting sustained high blood pressures in the penis sufficient to cause rigidity. Muscles in the perineum also assist in creating and maintaining penile rigidity. Erection may be induced centrally in the nervous system by sexual thoughts or fantasy, and is usually reinforced locally by reflex mechanisms. Erectile mechanics are substantially similar in the female for the clitoris. Impotence or male erectile dysfunction is defined as the inability to achieve and sustain an erection sufficient for intercourse. Impotence in any given case can result from psychological disturbances (psychogenic), from physiological abnormalities in general (organic), from neurological disturbances (neurogenic), hormonal deficiencies (endocrine) or from a combination of the foregoing. These descriptions are not exact, however. There is currently no standardized method of diagnosis or treatment. As used herein, psychogenic impotence is defined as functional impotence with no apparent overwhelming organic basis. It may be characterized by an ability to have an erection in response to some stimuli (e.g., masturbation, spontaneous nocturnal, spontaneous early morning, video erotica, etc.) but not others (e.g., partner or spousal attention). Various methods for the treatment of impotence have been suggested, including external devices, for example, tourniquets (see U.S. Pat. No. 2,818,855). In addition, penile implants, such as hinged or solid rods and inflatable, spring driven or hydraulic models, have been used for some time. The administration of erection effecting and enhancing drugs is taught in U.S. Pat. No. 4,127,118 to LaTorre. That patent teaches a method of treating male impotence by injecting into the penis an appropriate vasodilator, in particular, an adrenergic blocking agent or a smooth muscle relaxant to effect and enhance an erection. More recently, U.S. Pat. No. 4,801,587 to Voss et al. teaches the application of an ointment to relieve impotence. The ointment consists of the vasodilators papaverine, hydralazine, sodium nitroprusside, phenoxybenzamine, or phentolamine and a carrier to assist absorption of the primary agent through the skin. U.S. Pat. No. 5,256,652 to El-Rashidy teaches the use of an aqueous topical composition of a vasodilator such as papaverine together with hydroxypropyl-.beta.-cyclodextrin. Sexual functions in females can be divided into several broad areas: desire, arousal, and orgasm. Studies have indicated that up to 63% of women exhibit dysfunctions in either arousal or orgasmic stages of sexual activities (Frank E, et al., 1978. N Engl J Med 299: 111). Sexual disorders such as dyspareunia and vaginismus, reduce the arousal phase of female sexual functioning. Impaired clitoral responsiveness can lead to orgasmic disorders. The prevalence of female sexual dysfunction increases with age (Goldstein M and Teng N. 1991, Clin Geriatr Med 7:41; Thirlaway K et al., 1996. Quality of Life Res 5:81; Slob A et al., 1990, J Sex Martial Ther 16:59). Vascular risk factors of coronary diseases also increase the probability of sexual dysfunction in postmenopausal females (Sadeghi-Nejad H et al., 1996, J Urol 155:677A). Female sexual dysfunction can be due to an impairment in endothelium dependent vasodilation and smooth muscle relaxation which in turn could lead to impairment of vascular dependent events associated with sexual functioning. During sexual arousal, an increase in vaginal blood flow occurs which in turn results in vaginal lengthening and enhanced production of vaginal fluid. Enhanced clitoral blood flow occurs during arousal leading to clitoral engorgement and erection. Impairment of these vascular dependent events can lead to impairment in vaginal lubrication and/or a diminution in vaginal enlargement during the arousal stage of female sexual function. An abnormality in these vascular dependent events could impair the arousal and/or orgasmic phases of sexual functioning.